Differentiation of Testis Xenografts in the Prepubertal Marmoset Depends on the Sex and Status of the Mouse Host

Abstract

This study investigates the effects of the endocrine milieu of immunodeficient mouse host (intact vs. castrated male, intact male vs. intact female) on prepubertal marmoset (Callithrix jacchus) testicular xenografts. Previous marmoset xenografting studies used castrated nude mouse hosts which did not support efficient graft survival and maturation. Due to the distinct endocrine milieu in marmosets with a deletion of exon 10 in the LH receptor, we wanted to explore whether the most efficient xenograft development occurs in intact male mouse hosts compared to intact females or castrated males. We xenografted freshly isolated tissue from prepubertal marmosets (age range 4–6 months) into the back skin of three groups of nude mice (intact male, castrated male, and intact female). We collected serum for endocrine determinations and grafts after 20 weeks and determined hormonal/reproductive status, graft survival, somatic cell development and initiation of germ cell differentiation. Graft development, tubular integrity, and germ cell differentiation status in the grafts retrieved from different hosts was scored by morphometric analysis. The influence of the different endocrine status was compared between groups of hosts. Endocrine readouts and histological endpoints in xenografts substantiate that grafts were exposed to different microenvironments and responded with host specific developmental patterns. The intact male hosts supported the most significant progression of germ cell development. Our data provide evidence for the important role of the host milieu on survival and differentiation of marmoset xenografts. The xenografting model offers innovative avenues to exploit development and endocrine effects in the primate marmoset testis using limited numbers of non-human primates for the experimental settings.

Fertility Preservation in Childhood Cancer: Endocrine Activity in Prepubertal Human Testis Xenografts Exposed to a Pubertal Hormone Environment

“…To evaluate the effect of testosterone on AMH in AR-positive prepubertal testicular grafts, we took advantage of intact mice, which produce intratesticular testosterone. Seminal vesicle weights were within the normal range for intact adult mice [ 56 , 57 ], indicating that intratesticular xenografts were exposed to testosterone produced from host mice. Furthermore, AR expression was induced/maintained in xenografts indicating acquisition of androgen-sensitivity.…”

Downregulation of circLPAR3 inhibits tumor progression and glycolysis by liberating miR‐144‐3p and upregulating LPCAT1 in oral squamous cell carcinoma

“…The obtained xenograft tumors were fixed with 4% formaldehyde and then embedded in paraffin. Immunohistochemistry (IHC) analysis was carried out as previously described 21 . Primary antibodies included LPCAT1 (ab166903, Abcam) and PCNA (ab92552, Abcam).…”

“…Immunohistochemistry (IHC) analysis was carried out as previously described. 21 Primary antibodies included LPCAT1 (ab166903, Abcam) and PCNA (ab92552, Abcam). showed an overt upregulation of circLPAR3 in OSCC samples when compared to corresponding normal samples (Figure 1A).…”

FERTILITY PRESERVATION: Testicular transplantation for fertility preservation: clinical potential and current challenges

“…The endocrine status of the host animal may also be important as indicated by a recent study using marmoset prepubertal testis xenografts. When comparing intact males with castrate males or intact females as host mice, the most favourable results for germ cell development were achieved in the intact males (Sharma et al 2018).…”